Characterization<i>CSMD1</i>in a large set of primary lung, head and neck, breast and skin cancer tissues

Ma, Changqing; Quesnelle, Kelly M.; Sparano, Anthony; Rao, Shilpa; Park, Min S; Cohen, Marc A.; Wang, Yan; Samanta, Minu; Kumar, Madhu; Aziz, Meraj; Naylor, Tara L.; Weber, Barbara; Fakharzadeh, Steven; Weinstein, Gregory S.; Vachani, Anil; Feldman, Michael D.; Brose, Marcia S.

doi:10.4161/cbt.8.10.8132

Cited by 85 publications

(64 citation statements)

References 24 publications

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“…In contrast, 2 focal losses on chromosome 8 (13%, q = 1.03 × 10 ), encompassing 24 genes, were only observed in Trp53-null NRAS Q61K lesions ( Figure 2C). Interestingly, Csmd1 is a tumor suppressor frequently deleted and mutated in human melanoma and is commonly lost in many other tumor types (26). Overall, these data indicate that broad and focal CNAs are likely to influence the progression of BRAF V600E -and NRAS…”

Section: Q61kmentioning

confidence: 77%

Comparative oncogenomics identifies tyrosine kinase FES as a tumor suppressor in melanoma

Olvedy¹,

Tisserand²,

Luciani³

et al. 2017

Journal of Clinical Investigation

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Section: Q61kmentioning

confidence: 77%

Comparative oncogenomics identifies tyrosine kinase FES as a tumor suppressor in melanoma

Olvedy¹,

Tisserand²,

Luciani³

et al. 2017

Journal of Clinical Investigation

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“…A study (Yu et al 2010). This region of Chromosome 8 has also been identified as a peak region of deletion across multiple tumor types and contains the tumor suppressor CSMD1 (Ma et al 2009;Midorikawa et al 2009;Zack et al 2013). In light of these preexisting data, it seems likely that CNVs in this region occur more frequently, and perhaps provide a selective advantage, at the somatic level.…”

Section: Characteristics Of Somatic Cnvsmentioning

confidence: 97%

Assessment of megabase-scale somatic copy number variation using single-cell sequencing

2016

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Megabase-scale copy number variants (CNVs) can have profound phenotypic consequences. Germline CNVs of this magnitude are associated with disease and experience negative selection. However, it is unknown whether organismal function requires that every cell maintain a balanced genome. It is possible that large somatic CNVs are tolerated or even positively selected. Single-cell sequencing is a useful tool for assessing somatic genomic heterogeneity, but its performance in CNV detection has not been rigorously tested. Here, we develop an approach that allows for reliable detection of megabase-scale CNVs in single somatic cells. We discover large CNVs in 8%-9% of cells across tissues and identify two recurrent CNVs. We conclude that large CNVs can be tolerated in subpopulations of cells, and particular CNVs are relatively prevalent within and across individuals.[Supplemental material is available for this article.]Copy number variants (CNVs) can range in size from hundreds to millions of base pairs. Copy number changes affect approximately seven times as many base pairs as single-nucleotide variants and are major contributors to inter-individual differences (Sudmant et al. 2015). More than 65% of individuals harbor a germline CNV of at least 100 kb, and at least 1% of individuals have a CNV exceeding 1 Mb (Itsara et al. 2009). Although megabase-scale CNVs could be considered collectively common, the specific CNVs themselves are rare and often associated with disease (Girirajan et al. 2011). Not surprisingly, large CNVs experience negative selection, and their existence in a population is largely due to de novo events (Itsara et al. 2010).Although germline, megabase-scale CNVs are found in 1% of individuals, the prevalence of somatic CNVs is only beginning to be investigated. Array-based analyses of populations of cells from many individuals provided initial insight into this question. These studies identified megabase-scale somatic aberrations in up to 4% of individuals; however, the sensitivity was limited to CNVs present in >5% of cells (Forsberg et al. 2012;Jacobs et al. 2012;Laurie et al. 2012). These studies are thus blind to alterations that arise late in development or adversely affect fitness, as this would limit their propagation in a cell population. With the emergence of methods to amplify the genome of a single cell, single-cell sequencing now provides an alternate means of assessing the prevalence of somatic CNVs and offers the advantage of detecting variants that exist in as few as one cell. Recently, two groups performed low-coverage sequencing of single human neurons and reported at least one megabase-scale CNV in >40% of neurons (McConnell et al. 2013;Cai et al. 2014). These findings suggest much greater tolerance of large somatic CNVs compared to germline CNVs and raise the interesting possibility that somatic genomic heterogeneity contributes to phenotypic diversity within a tissue. However, it is still unclear how CNV detection methods perform when applied to individual cells, as single-cell sequ...

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“…It is possible that the small sample size (5 and 4 patients, respectively) was a factor. CDKN2A, PTPRO, and CSMD1 have previously been identified as tumor suppressors in multiple cancers [34][35][36][37] and are epigenetically silenced by DNA hypermethylation in ALL, 38 chronic lymphocytic leukemia, 8 hepatocellular carcinoma, 36 lung cancer, 37 and squamous cell carcinoma. 39 For these genes, promoter hypermethylation correlated with down-regulation of mRNA expression, and expression of these genes could be reactivated by treatment with 5-azacytidine.…”

Section: Genomic Analysis Of Relapsed Childhood Leukemia 5223mentioning

confidence: 99%

Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies

Hogan

Meyer

Yang

et al. 2011

Blood

181

220

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Despite an increase in survival for children with acute lymphoblastic leukemia (ALL), the outcome after relapse is poor. To understand the genetic events that contribute to relapse and chemoresistance and identify novel targets of therapy, 3 high-throughput assays were used to identify genetic and epigenetic changes at relapse. Using matched diagnosis/ relapse bone marrow samples from children with relapsed B-precursor ALL, we evaluated gene expression, copy number abnormalities (CNAs), and DNA methylation. Gene expression analysis revealed a signature of differentially expressed genes from diagnosis to relapse that is different for early (< 36 months) and late (> 36 months) relapse. CNA analysis discovered CNAs that were shared at diagnosis and relapse and others that were new lesions acquired at relapse. DNA methylation analysis found increased promoter methylation at relapse. There were many genetic alterations that evolved from diagnosis to relapse, and in some cases these genes had previously been associated

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CharacterizationCSMD1in a large set of primary lung, head and neck, breast and skin cancer tissues

Cited by 85 publications

References 24 publications

Comparative oncogenomics identifies tyrosine kinase FES as a tumor suppressor in melanoma

Comparative oncogenomics identifies tyrosine kinase FES as a tumor suppressor in melanoma

Assessment of megabase-scale somatic copy number variation using single-cell sequencing

Integrated genomic analysis of relapsed childhood acute lymphoblastic leukemia reveals therapeutic strategies

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